Several lines of evidence supporting the theory of nuclear equivalence are consistent with the view that specialized cell types of adults contain the complete set of genes derived from fertilized eggs; however, conclusive proof is still lacking. Amphibian nuclear transplantation has been the most stringent test of this theory. When nuclei from early embryos are transplanted into eggs, the eggs develop normally. However, only a few nuclei from normal adult cells or from the renal carcinoma (herpesvirus etiology) promote eggs to develop into abnormal tadpoles. In the previous grant, I proposed that nuclei from advanced cell types might be conditioned in oocytes and their genetic potential enhanced. We have established that this hypothesis is tenable. First, blastula nuclei injected into oocytes support development through embryogenesis, indicating that the oocyte can be used to test the developmental potential of nuclei. Second, nuclei from non-cycling and terminally differentiated erythrocytes that do not synthesize DNA in eggs will reverse and synthesize DNA following conditioning in oocytes, indicating that the critical test of the theory of nuclear equivalence can now be pursued in the oocyte. The current application proposes: 1) to test the developmental potential of nuclei from determined and specialized cells and from the renal carcinoma by first conditioning nuclei in oocytes; and 2) to investigate mechanisms responsible for the reversibility of nuclei conditioned in oocytes. If a significant number of normal frogs develop, the nuclear totipotency of normal specialized cells and the renal carcinoma would be demonstrated. Such results would: 1) prove the theory of nuclear equivalence in normal differentiation; and 2) demonstrate that viral carcinogenesis of this tumor has an epigenetic origin and the cells can therefore be reversed from malignancy to normalcy with proper environmental conditions.